1. Field of Invention
The present invention relates to devices and methods for capturing rare cells.
2. Background Information
Cancer is one of the leading causes of death in the developed world, resulting in over 500,000 deaths per year in the United States alone. Over one million people are diagnosed with cancer in the U.S. each year, and overall it is estimated that more than 1 in 3 people will develop some form of cancer during their lifetime.
Most cancer patients are not killed by their primary tumor. Instead, cancer patients succumb to metastases: the spread of malignant cells from one part of the body to another. If a primary tumor is detected early enough, it can often be eliminated by surgery, radiation, chemotherapy or some combination of these treatments. In contrast, metastatic tumors are difficult to detect and treatment becomes more challenging as metastases progresses. As such, there is a need to develop methods for detecting early-stage cancer metastasis.
Cancer cells that break away from the primary tumor site are known as circulating tumor cells (CTCs).1 CTCs represent a potential alternative to invasive biopsies as a source of tumor tissue for the detection, characterization, and monitoring of non-hematologic cancers.2-4 Over the past decade, CTCs have become an emerging “biomarker” for detecting early-stage cancer metastasis, predicting patient prognosis, as well as monitoring disease progression and therapeutic outcomes of cancer.5 However, isolation of CTCs have been technically challenging due to the extremely low abundance (a few to hundreds per mL) of CTCs among a high number of hematologic cells (109 cells/mL) in the blood.4,6,7 
Previous approaches for enriching or sorting CTCs from peripheral blood include flow cytometry, immunomagnetic beads, high-throughput optical-imaging systems, and fibre optic array scanning. Immunomagnetic-bead purification of CTCs is currently the most widely used technology in the clinical setting, and has successfully identified CTCs in patients with lung, prostate, colon, breast, and pancreatic cancer.3,4,8-10 However, this approach isolates small numbers of CTCs (4±24 (mean±s.d.) per ml in lung; 11±118 in breast; 10±33 in prostate; and 1±2 in both colorectal and pancreatic cancers)3 with very low purity (0.01-0.1%)10, and low yield (˜20-60% of patients)3. The level of “biological noise” associated with the low sensitivity, selectivity, and yield of immunomagnetic-bead technologies restricts their use in early cancer detection and in monitoring patient response to treatment. At present, immunomagnetic-bead technology is useful as a gross prognostic tool, classifying patients into high- and low-risk categories.5 
Microfluidic lab-on-a-chip devices provide unique opportunities for cell sorting and rare-cell detection. Microfluidic technology has been successfully used for microfluidic flow cytometry, continuous size-based separation11 and chromatographic separation12; however, these methods are unable to process large sample volumes (e.g., milliliters of whole blood)13. Microfluidic technology has also been used to capture CTCs from whole blood samples.8,9 However, existing CTC-capture systems require complicated fluidic handling systems to introduce blood flow through the devices. Furthermore, these systems use microstructures, which are not optimal for cell capture, to isolate CTCs.
The surfaces of most tumor cells of epithelial origin (carcinomas) are covered with nanoscaled microvilli of variable sizes and configuration.14 In benign epithelial cells of glandular origin, the microvilli are polarized (i.e., confined to one aspect of the normal cell, usually that facing the lumen of a gland or organ) and are of uniform and monotonous configuration. The microvilli of epithelial cancer cells cover the entire cell surface, vary in size and length, and sometimes form clumps of very long microvilli. In some tumors, notably carcinomatous mesothelioma, tufts of long microvilli characterize the malignant cells. Furthermore, additional structures are present on the cell surface, which are also nanoscale in size, including lamellipodia, filopodia, and lipid-rail molecular groups. Some embodiments of the present invention proposes a new generation of cell capture devices that takes advantage of the presence of these nanoscaled structures on the cell surface.